Neurobehavioral assessments, including arousal activity level and sleep pattern, are endpoints of global nervous system function. Virtually all pathological conditions, particularly neuropsychological disorders such as anxiety and depression, and a variety of different classes of drugs, can lead to the alteration of behavior and disturbance of sleep. Although a battery of behavioral assessments is frequently conducted in animals exposed to new compounds or in genetically altered mice (e.g., gene knockout), sleep assessments are rarely performed in these subjects because of the technical difficulty of using electroencephalographs (EEGs) and electromyographs (EMGs). In general, behavioral assessments and drug behavioral safety and efficacy screening in animals have become a bottleneck in the modern drug discovery process because of the lack of high-throughput screening (HTS) tools available. Promising results obtained in our SBIR Phase I feasibility study have demonstrated that the non-invasive piezoelectric (piezo)-system is not only capable of monitoring sleep/wake activity, but can also detect abnormal behavior such as tremors and seizures in mice. In the proposed Phase II project, we will expand this novel approach by incorporating other proven biosensor technologies (e.g., imaging tracking and force transducers) into an individual piezo-homecage to create a flexible and comprehensive behavioral assay toolkit. Our specific aims are to (1) extend the current piezo monitoring application by integrating it with other biosensors, (2) refine algorithms for pattern recognition of characteristic behavior and improve software to enable fully automated data analysis, and (3) validate this novel system with pharmacological studies in mice and by comparison with conventional methods. Multiple behavioral parameters generated from this non-invasive and efficient homecage monitor will provide integrated information about agent or gene mutant effects on specialized functions of the animal. This versatile system will provide a high-throughput in vivo screening tool that can accelerate the complex process of new drug discovery and ultimately help to identify safer and more effective therapeutic agents.